This study is a continuation of a project that was initiated last year with the support of the TSA. The genetic basis of TS remains elusive. Nevertheless several genomic regions have been implicated. We have focused our efforts on the evaluation of a DNA region close to the end of the long arm of chromosome 17 (17q25) as a candidate susceptibility region for TS. Our results so far are quite encouraging. In a study of four large multigenerational families with multiple individuals affected with TS we obtained positive association and linkage results with multiple genetic markers in this interval. Study of an independent sample of small nuclear families with one or two affected children (provided by the Toronto Western Reseach Institute) also produced positive findings. To further narrow down the large candidate interval, we will now increase the density of the tested polymorphic markers. Based on what we know about their function, the region will be screened for genes that may be involved in the development of TS. We will also attempt to reproduce our results in three independent samples of families with one or two children with TS and their parents. Two of these samples will be made available to us through our collaboration with the Toronto Western Reseach Institute and Semmelweis University in Hungary. The third sample is the Tourette Syndrome Association International Consortium for Genetics’ (TSAICG) sample of families with two affected sibs, that provided one of the initial findings of linkage of TS to 17q25. The detailed clinical information available for the affected individuals in these samples will allow us to test for possible association of the studied region with specific aspects of TS. The regions that produce the strongest indications for genetic linkage and/or association with TS will be screened for polymorphisms of possible functional significance. In short the proposed study is a comprehensive investigation of the possible involvement of 17q25 in the development of TS. Peristera Paschou, Ph.D. Yale University School of Medicine, New Haven, CT Award: $73,308 (Year 2 Award) This award has ben funded through the generosity of the Ochsman Family Foundation Tourette Association of America Inc. – Research Grant Award 2004-2005